Edar is a downstream target of beta-catenin and drives collagen accumulation in the mouse prostate
Beta-catenin (CTNNB1) directs ectodermal appendage spacing by activating ectodysplasin A receptor (EDAR) transcription, but whether CTNNB1 acts by a similar mechanism in the prostate, an endoderm-derived tissue, is unclear. Here we examined the expression, function, and CTNNB1 dependence of the EDAR...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
The Company of Biologists
2019-03-01
|
| Series: | Biology Open |
| Subjects: | |
| Online Access: | http://bio.biologists.org/content/8/3/bio037945 |
| _version_ | 1819075556407246848 |
|---|---|
| author | Kyle A. Wegner Vatsal Mehta Jeanette A. Johansson Brett R. Mueller Kimberly P. Keil Lisa L. Abler Paul C. Marker M. Mark Taketo Denis J. Headon Chad M. Vezina |
| author_facet | Kyle A. Wegner Vatsal Mehta Jeanette A. Johansson Brett R. Mueller Kimberly P. Keil Lisa L. Abler Paul C. Marker M. Mark Taketo Denis J. Headon Chad M. Vezina |
| author_sort | Kyle A. Wegner |
| collection | DOAJ |
| description | Beta-catenin (CTNNB1) directs ectodermal appendage spacing by activating ectodysplasin A receptor (EDAR) transcription, but whether CTNNB1 acts by a similar mechanism in the prostate, an endoderm-derived tissue, is unclear. Here we examined the expression, function, and CTNNB1 dependence of the EDAR pathway during prostate development. In situ hybridization studies reveal EDAR pathway components including Wnt10b in the developing prostate and localize these factors to prostatic bud epithelium where CTNNB1 target genes are co-expressed. We used a genetic approach to ectopically activate CTNNB1 in developing mouse prostate and observed focal increases in Edar and Wnt10b mRNAs. We also used a genetic approach to test the prostatic consequences of activating or inhibiting Edar expression. Edar overexpression does not visibly alter prostatic bud formation or branching morphogenesis, and Edar expression is not necessary for either of these events. However, Edar overexpression is associated with an abnormally thick and collagen-rich stroma in adult mouse prostates. These results support CTNNB1 as a transcriptional activator of Edar and Wnt10b in the developing prostate and demonstrate Edar is not only important for ectodermal appendage patterning but also influences collagen organization in adult prostates. This article has an associated First Person interview with the first author of the paper. |
| first_indexed | 2024-12-21T18:27:17Z |
| format | Article |
| id | doaj.art-469cf7752b1946f9b7faee988ecbd3f1 |
| institution | Directory Open Access Journal |
| issn | 2046-6390 |
| language | English |
| last_indexed | 2024-12-21T18:27:17Z |
| publishDate | 2019-03-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Biology Open |
| spelling | doaj.art-469cf7752b1946f9b7faee988ecbd3f12022-12-21T18:54:23ZengThe Company of BiologistsBiology Open2046-63902019-03-018310.1242/bio.037945037945Edar is a downstream target of beta-catenin and drives collagen accumulation in the mouse prostateKyle A. Wegner0Vatsal Mehta1Jeanette A. Johansson2Brett R. Mueller3Kimberly P. Keil4Lisa L. Abler5Paul C. Marker6M. Mark Taketo7Denis J. Headon8Chad M. Vezina9 Molecular and Environmental Toxicology Center University of Wisconsin-Madison, Madison, WI 53706, USA Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, WI 53706, USA The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh EH25 9RG, United Kingdom Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, WI 53706, USA Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, WI 53706, USA Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, WI 53706, USA School of Pharmacy, University of Wisconsin-Madison, Madison, WI 53706, USA Division of Experimental Therapeutics, Graduate School of Medicine, Kyoto University Yoshida-Konoé-cho, Sakyo, Kyoto 606-8501, Japan The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh EH25 9RG, United Kingdom Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, WI 53706, USA Beta-catenin (CTNNB1) directs ectodermal appendage spacing by activating ectodysplasin A receptor (EDAR) transcription, but whether CTNNB1 acts by a similar mechanism in the prostate, an endoderm-derived tissue, is unclear. Here we examined the expression, function, and CTNNB1 dependence of the EDAR pathway during prostate development. In situ hybridization studies reveal EDAR pathway components including Wnt10b in the developing prostate and localize these factors to prostatic bud epithelium where CTNNB1 target genes are co-expressed. We used a genetic approach to ectopically activate CTNNB1 in developing mouse prostate and observed focal increases in Edar and Wnt10b mRNAs. We also used a genetic approach to test the prostatic consequences of activating or inhibiting Edar expression. Edar overexpression does not visibly alter prostatic bud formation or branching morphogenesis, and Edar expression is not necessary for either of these events. However, Edar overexpression is associated with an abnormally thick and collagen-rich stroma in adult mouse prostates. These results support CTNNB1 as a transcriptional activator of Edar and Wnt10b in the developing prostate and demonstrate Edar is not only important for ectodermal appendage patterning but also influences collagen organization in adult prostates. This article has an associated First Person interview with the first author of the paper.http://bio.biologists.org/content/8/3/bio037945ProstateUrogenital sinusCTNNB1WNT10BEDARCollagen |
| spellingShingle | Kyle A. Wegner Vatsal Mehta Jeanette A. Johansson Brett R. Mueller Kimberly P. Keil Lisa L. Abler Paul C. Marker M. Mark Taketo Denis J. Headon Chad M. Vezina Edar is a downstream target of beta-catenin and drives collagen accumulation in the mouse prostate Biology Open Prostate Urogenital sinus CTNNB1 WNT10B EDAR Collagen |
| title | Edar is a downstream target of beta-catenin and drives collagen accumulation in the mouse prostate |
| title_full | Edar is a downstream target of beta-catenin and drives collagen accumulation in the mouse prostate |
| title_fullStr | Edar is a downstream target of beta-catenin and drives collagen accumulation in the mouse prostate |
| title_full_unstemmed | Edar is a downstream target of beta-catenin and drives collagen accumulation in the mouse prostate |
| title_short | Edar is a downstream target of beta-catenin and drives collagen accumulation in the mouse prostate |
| title_sort | edar is a downstream target of beta catenin and drives collagen accumulation in the mouse prostate |
| topic | Prostate Urogenital sinus CTNNB1 WNT10B EDAR Collagen |
| url | http://bio.biologists.org/content/8/3/bio037945 |
| work_keys_str_mv | AT kyleawegner edarisadownstreamtargetofbetacateninanddrivescollagenaccumulationinthemouseprostate AT vatsalmehta edarisadownstreamtargetofbetacateninanddrivescollagenaccumulationinthemouseprostate AT jeanetteajohansson edarisadownstreamtargetofbetacateninanddrivescollagenaccumulationinthemouseprostate AT brettrmueller edarisadownstreamtargetofbetacateninanddrivescollagenaccumulationinthemouseprostate AT kimberlypkeil edarisadownstreamtargetofbetacateninanddrivescollagenaccumulationinthemouseprostate AT lisalabler edarisadownstreamtargetofbetacateninanddrivescollagenaccumulationinthemouseprostate AT paulcmarker edarisadownstreamtargetofbetacateninanddrivescollagenaccumulationinthemouseprostate AT mmarktaketo edarisadownstreamtargetofbetacateninanddrivescollagenaccumulationinthemouseprostate AT denisjheadon edarisadownstreamtargetofbetacateninanddrivescollagenaccumulationinthemouseprostate AT chadmvezina edarisadownstreamtargetofbetacateninanddrivescollagenaccumulationinthemouseprostate |